Project 1. Kirk P. Conrad PI. The overarching hypothesis of the proposed Program Project is that pregnancies conceived by ART begin in a state, which is not physiological for the mother, secondary to the abnormal status of the corpus luteum, its producfion of relaxin or other hormones. The corpus luteum and maternal circulating relaxin may be absent altogether, or there may be multiple corpora lutea and supraphysiological concentrafions of relaxin depending on the ART protocol. Kirk P. Conrad PI and colleagues in Project I propose that these abnormalities of the corpus luteum in ART, which are often iatrogenically imposed, compromise optimal maternal cardiovascular adaptations during pregnancy (also see Project 11). This novel hypothesis is founded upon tantalizing and provocafive, yet compelling preliminary evidence from both animal and human studies. Dr. Conrad and coworkers propose a comprehensive explorafion of maternal cardiovascular adaptations in women conceiving by ART in the University of Florida CTSI. Aim 1 will focus on maternal systemic hemodynamics and arterial mechanical properties, renal funcfion and volume status. Aim 2 will invesfigate maternal baroreflex funcfion. Thus, we will be able to ascertain whether relaxin or other corpus luteal product(s) supports optimal maternal cardiovascular adaptations during eariy and late pregnancy. If maternal cardiovascular adaptations during pregnancy are abnormal in ART pafients as we hypothesize, then this could contribute to the increased incidence of adverse pregnancy outcomes observed in these pafients such as compromised fetal growth and pregnancy induced hypertension (see Project 111). When ovarian funcfion is absent or suppressed, and circulafing relaxin is absent, relaxin supplementation might be warrented. Alternatively, in the case of ovarian stimulation, less sfimulafion might be recommended, in order to reduce the number of corpora lutea, and thus, circulating relaxin. Finally, if maternal cardiovascular adaptations to pregnancy are normal in ART pafients, then this outcome should be reassuring to both REI physicians and their patients. RELEVANCE (See instructions): Emerging evidence suggests that ART is associated with increased risk for adverse pregnancy outcomes. In Project 1, we propose to test a new concept that may contribute to this increased risk. That is, we hypothesize that pregnancies conceived by ART begin in a state, which is not physiological for the mother secondary to the abnormal status of the ovary and its hormones. This, in turn, compromises maternal cardiovascular adapatafions to pregnancy, thereby predisposing to adverse pregnancy outcomes.